CD14 polymorphisms and serum CD14 levels through childhood: a role for gene methylation?
| Autor: | Berit Granum, Tale Mæhre Torjussen, Dag E. Undlien, Robert Lyle, Hanne Sagsveen Hjorthaug, Kai-Håkon Carlsen, Kristina Gervin, Monica Cheng Munthe-Kaas, Karin C. Lødrup Carlsen |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Linkage disequilibrium Time Factors Genotype Immunology Lipopolysaccharide Receptors Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Immunology and Allergy SNP Humans Epigenetics Prospective Studies Child Genetic Association Studies Infant Newborn Gene Expression Regulation Developmental Methylation DNA DNA Methylation Fetal Blood Asthma Genotype frequency Child Preschool DNA methylation Female Follow-Up Studies |
| Zdroj: | The Journal of allergy and clinical immunology. 125(6) |
| ISSN: | 1097-6825 |
| Popis: | Background CD14 is a pattern-recognition receptor for environmental LPS, and engagement of the CD14-LPS complex activates innate host defense mechanisms. Single nucleotide polymorphisms (SNPs) in the CD14 gene have been associated with soluble CD14 (sCD14) levels, but inconsistencies between studies suggest the presence of regulatory mechanisms hitherto not well understood. Objective We sought to investigate possible associations between CD14 SNPs and sCD14 levels at different time points in childhood (at birth [cord blood] and 2 and 10 years) and to explore whether these associations were related to CD14 gene methylation. Methods Four SNPs, rs2569191 (−1145GA), rs5744455 (−550CT or −651CT), rs2569190 (−159CT or −260CT), and rs4914 in CD14 were genotyped in 762 children from the Environmental and Childhood Asthma study. Genotype frequencies were analyzed for association with sCD14 levels in 660 babies, 346 children at age 2 years, and 360 children at age 10 years. In a subgroup of 157 children with DNA available at both 2 and 10 years of age, CD14 methylation patterns were determined and analyzed against detected CD14 gene–sCD14 associations. Results rs2569191, rs5744455, and rs2569190 were associated with sCD14 levels at birth and 2 years, but only rs5744455 was associated with sCD14 levels at 10 years. CD14 methylation increased significantly from age 2 to 10 years, and the level of methylation was inversely correlated with sCD14 levels at 10 years. Conclusion The reduced effect of CD14 polymorphisms on sCD14 levels from early to late childhood paralleled a small but significant increase in CD14 methylation during the same period. |
| Databáze: | OpenAIRE |
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